Background Brucellosis is a common zoonotic infectious disease in China. This study aimed to investigate the incidence trends of brucellosis in China, construct an optimal prediction model, and analyze the driving role of climatic factors for human brucellosis. Methods Using brucellosis incidence, and the socioeconomic and climatic data for 2014–2020 in China, we performed spatiotemporal analyses and calculated correlations with brucellosis incidence in China, developed and compared a series of regression and Seasonal Autoregressive Integrated Moving Average X (SARIMAX) models for brucellosis prediction based on socioeconomic and climatic data, and analyzed the relationship between extreme weather conditions and brucellosis incidence using copula models. Results In total, 327,456 brucellosis cases were reported in China in 2014–2020 (monthly average of 3898 cases). The incidence of brucellosis was distinctly seasonal, with a high incidence in spring and summer and an average annual peak in May. The incidence rate was highest in the northern regions’ arid and continental climatic zones (1.88 and 0.47 per million people, respectively) and lowest in the tropics (0.003 per million people). The incidence of brucellosis showed opposite trends of decrease and increase in northern and southern China, respectively, with an overall severe epidemic in northern China. Most regression models using socioeconomic and climatic data cannot predict brucellosis incidence. The SARIMAX model was suitable for brucellosis prediction. There were significant negative correlations between the proportion of extreme weather values for both high sunshine and high humidity and the incidence of brucellosis as follows: high sunshine, $$r$$ r = −0.59 and −0.69 in arid and temperate zones; high humidity, $$r$$ r = −0.62, −0.64, and −0.65 in arid, temperate, and tropical zones. Conclusions Significant seasonal and climatic zone differences were observed for brucellosis incidence in China. Sunlight, humidity, and wind speed significantly influenced brucellosis. The SARIMAX model performed better for brucellosis prediction than did the regression model. Notably, high sunshine and humidity values in extreme weather conditions negatively affect brucellosis. Brucellosis should be managed according to the “One Health” concept.
Purpose of review This review focuses on recent efforts in identifying with-no-lysine kinase 4 (WNK4) as a physiological intracellular chloride sensor and exploring regulators of intracellular chloride concentration ([Cl-]i) in the distal convoluted tubule (DCT). Recent findings The discovery of WNK1's chloride-binding site provides the mechanistic details of the chloride-sensing regulation of WNK kinases. The subsequent in-vitro studies reveal that the chloride sensitivities of WNK kinases were variable. Because of its highest chloride sensitivity and dominant expression, WNK4 emerges as the leading candidate of the chloride sensor in DCT. The presentation of hypertension and increased sodium-chloride cotransporter (NCC) activity in chloride-insensitive WNK4 mice proved that WNK4 is inhibitable by physiological [Cl-]i in DCT. The chloride-mediated WNK4 regulation is responsible for hypokalemia-induced NCC activation but unnecessary for hyperkalemia-induced NCC deactivation. This chloride-sensing mechanism requires basolateral potassium and chloride channels or cotransporters, including Kir4.1/5.1, ClC-Kb, and possibly KCCs, to modulate [Cl-]i in response to the changes of plasma potassium. Summary WNK4 is both a master NCC stimulator and an in-vivo chloride sensor in DCT. The understanding of chloride-mediated regulation of WNK4 explains the inverse relationship between dietary potassium intake and NCC activity.
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